Children with autism spectrum disorders (ASD) are characterized by deficits in social interaction, impaired communication, and repetitive and stereotyped patterns of behavior, interests, and activities (APA, 1994). Interest in the amelioration of some of the core and secondary features of ASD has led the use of a wide range of pharmacological interventions, with inattention and overactivity, ritualistic behavior, self-injury and agitation/aggression among the most frequently targeted symptoms. Recent survey data indicates that up to 34 percent of individuals with ASD are prescribed medication and/or vitamins for control of a wide range of behaviors (Aman et al., 1995). While most pharmacological research to date has attempted to treat many of the behavioral deficits commonly associated with ASD, few pharmacological studies have attempted to ameliorate the core features of this disorder (an area of particular interest for this RFA). Donepezil HC1, a cholinesterase inhibitor which increases brain levels of acetylcholine, is purported to enhance cognitive functioning in a range of disorders, including multiple sclerosis, Alzheimer's disorder, and ADHD. A recent open-label study of the safety and efficacy of donepezil HC1 in 25boys with ASD found significantly increased speech production and a statistical trend toward improvement in core symptoms of ASD (Chez et al., 2000). The present application will provide an opportunity to conduct further pilot testing of the tolerability, safety and effect of donepezil HCl on the cognitive deficits presumed to underlie the core features of ASD. Forty children and adolescents with ASD will be recruited to participate in a 10-week, double blind, placebo-controlled parallel groups study of donepezil HC1. This feasibility study is designed to provide documentation of medication-enhanced cognitive functioning in ASD using a 5mg and 10 mg/day donepezil HC1 dose. This study will also examine the side effects profile of donepezil HC1 in children with ASD, explore possible correlates of treatment response, and provide an opportunity to obtain initial pilot data to determine the sample size needed to conduct a full-scale intervention trial.